Dicyclohexylcarbodiimide → 4-{[(R)-(1-aza-bicyclo[2.2.2]oct-3-yl)oxycarbonyl]-phenylamino-methyl}-benzoic acid methyl ester

HRID 77019노트

반응식

HRID 77019 반응식
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:12]([OH:14])=[O:13])=[CH:7][CH:6]=1)=[O:4].C(N(C(C)C)C(C)C)C.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[N:56]12[CH2:63][CH2:62][CH:59]([CH2:60][CH2:61]1)[C@@H:58](O)[CH2:57]2>C1COCC1>[CH3:1][O:2][C:3](=[O:4])[C:5]1[CH:6]=[CH:7][C:8]([CH:11]([C:12]([O:14][C@@H:58]2[CH:59]3[CH2:62][CH2:63][N:56]([CH2:61][CH2:60]3)[CH2:57]2)=[O:13])[NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:9][CH:10]=1

참가 물질

6

반응물 4

HCID 10868Dicyclohexylcarbodiimide2회HCID 757711-Hydroxybenzotriazole2회HCID 914043-Quinuclidinol, (-)-2회HCID 67425011N-ethyl-N-isopropylpropan-2-amine 2-(4-(methoxycarbonyl)phenyl)-2-(phenylamino)acetate

생성물 1

HCID 594011274-{[(R)-(1-aza-bicyclo[2.2.2]oct-3-yl)oxycarbonyl]-phenylamino-methyl}-benzoic acid methyl ester수율 21%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

N-Ethyl-N-isopropylpropan-2-amine 2-(4-(methoxycarbonyl)phenyl)-2-(phenylamino)acetate (I94) (212 mg, 0.51 mmol), DCC (158 mg, 0.77 mmol), and HOBT (117 mg, 0.77 mmol) are dissolved in dry THF (5 mL). (R)-Quinuclidin-3-ol (195 mg, 1.53 mmol) is added and the mixture is stirred at RT for 2 days. A second portion of DCC (79 mg, 0.38 mmol), HOBT (58.7 mg, 0.38 mmol) and (R)-quinuclidin-3-ol (98 mg, 0.77 mmol) are added and the mixture is further stirred for 24 hours. Then THF is evaporated, the residue is dissolved in EtOAc and washed with NaHCO3, water and brine. The organic phase is dried (Na2SO4), filtered and evaporated. The crude is purified by preparative HPLC. The recovered fractions are evaporated, dissolved in EtOAc and washed with sat. NaHCO3. The organic phase is dried (Na2SO4), filtered and evaporated to afford the desired compound as a colorless oil (42 mg, 21% yield, mixture of diastereoisomers).

후처리

  1. stirringthe mixture is further stirred for 24 hours
  2. customThen THF is evaporated
  3. dissolutionthe residue is dissolved in EtOAc
  4. washwashed with NaHCO3, water and brine
  5. dry with materialThe organic phase is dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude is purified by preparative HPLC
  9. customThe recovered fractions are evaporated
  10. dissolutiondissolved in EtOAc
  11. washwashed with sat. NaHCO3
  12. dry with materialThe organic phase is dried (Na2SO4)
  13. filtrationfiltered
  14. customevaporated

출처 및 근거

ORD 기록
ord-053149529fe2486694c57e1e39da6e07
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835682B2

반응 노트

불러오는 중…